Relationship Between the Expression of PD-1 and CTLA-4 on T Lymphocytes and the Severity and Prognosis of Sepsis

Lang Wang,1,2,&ast; Zhiqi Zhang,1,3,&ast; Xingxiang Chen,1 Fang Yu,4 Hai Huang,4 Xue Shen,4 Yujie Tan,4 Qingqing Wu4 1Department of Microbiology and Immunology, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, People’s Republic of China; 2Hunan University of Medicine, Huaihua, People’s Republic of China; 3Taian City Central Hospital Affiliated to Qingdao University, Taian, People’s Republic of China; 4Center of Clinical Laboratory, the Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingqing Wu, Center of Clinical Laboratory, the Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China, Email wuqingqing@gmc.edu.cnPurpose: The study aimed to investigate the relationship between the expression of PD-1 and CTLA-4 on the surface of peripheral blood T lymphocyte subsets in patients with sepsis and the severity and prognosis of the disease.Patients and Methods: The study included patients with sepsis who were admitted to the intensive care unit. The expression of PD-1 and CTLA-4 on T lymphocyte subsets was detected by flow cytometry, and the severity of sepsis was assessed using the SOFA score.Results: The expression of PD-1 on CD4+T cells, PD-1 on Tregs, and CTLA-4 on Tregs increased with the severity of the disease (P< 0.05). Multivariate logistic regression analysis showed that PD-1 expression on CD4+T cells, CTLA-4 expression on Tregs, and the SOFA score were independent risk factors for 28-day mortality in patients with sepsis (P< 0.05). The area under the curve of the SOFA score combined with the expression of PD-1 on CD4+T cells and CTLA-4 on Treg cells was significantly higher than any single indicator (P< 0.05). Patients with high expression of PD-1 on CD4+T cells (> 31.25%) and CTLA-4 on Tregs (> 12.64%) had a lower 28-day survival rate (P< 0.05).Conclusion: The increased expression of PD-1 and CTLA-4 on CD4+T cells and Tregs is significantly associated with the severity and prognosis of sepsis patients. The combination of the SOFA score and the expression of PD-1 on CD4+T cells and CTLA-4 on Tregs can further improve the prognostic predictive value. These findings may be promising biomarkers for prognostic assessment, risk stratification, and identification of immunosuppression in patients with sepsis.Keywords: sepsis, T lymphocyte subsets, programmed cell death receptor-1, cytotoxic T lymphocyte antigen-4, prognosis